Showing papers in "Journal of Gastrointestinal and Liver Diseases in 2011"

Helicobacter pylori in developing countries. World Gastroenterology Organisation Global Guideline.

Abstract: Helicobacter pylori (Hp) is found in half the population of the world. Its prevalence is highly variable in relation to geography, ethnicity, age, and socioeconomic factors high in developing countries and lower in the developed world. In general, however, there has been a decreasing trend in the prevalence of Hp in many parts of the world in recent years. Direct epidemiologic comparisons of peptic ulcer disease (PUD) between developing and developed countries are complex, as peptic ulcers may be asymptomatic and the availability and accessibility of the tests required for diagnosis vary widely. In developing countries, Hp infection is a public-health issue. The high prevalence of the infection means that public-health interventions may be required. Therapeutic vaccination is probably the only strategy that would make a decisive difference in the prevalence and incidence of Hp throughout the world. The short-term approach, however provided that resources allow for this would be a test-andtreat strategy for those who are at risk for peptic ulcer disease or gastric cancer, as well as for those with troublesome dyspepsia. EDuCATION IN GASTROENTEROLOGy

Quality of life in Coeliac Disease is determined by perceived degree of difficulty adhering to a gluten-free diet, not the level of dietary adherence ultimately achieved.

Abstract: Background: Coeliac Disease (CD) is an increasingly common autoimmune condition, the treatment of which is a gluten-free diet (GFD). Previous studies fail to reach consensus of the impact this restrictive diet has on an individual’s quality of life (QoL). Furthermore, how patient characteristics, such as demographic and educational background, may predict GFD adherence is poorly understood. We aimed to assess which factors had an impact on Qol in patients with CD. methods: Case-control postal survey (n=573). Biopsy-proven CD patients (n=225; mean disease duration 8yrs; range 0.5-52yrs; male 26%) and age and sex matched controls (n=348; male 36%) completed The Short-Form 36-Item (SF-36) QoL measure, The Hospital Anxiety & Depression Scale (HADS), GFD assessment, and demographic questionnaire. Results: We found a high proportion of GFD adherence: ‘Full Adherence’ 65%, ‘Partial Adherence’ 31%, ‘None Adherence’ 4%, accompanied however, by 80% of patients reporting difficulty adhering to the GFD: ‘Impossible’ 5%, ‘Mostly difficult’ 14%, ‘Sometimes difficult’ 61%, ‘No difficulty’ 20%. Negligible differences in QoL scores were observed when comparing full versus partial/none GFD patients (P=>0.05), however, stepwise reductions in QoL and increasing likelihood of anxiety/depression were found in association with increasing degree of difficulty adhering to the GFD (P=<0.0001). Demographic assessment suggests that an affluent background and a university education promote greater GFD adherence. Conclusions: Most coeliac patients adhere to a GFD but encounter difficulty doing so (potentially influenced by social and educational background). The degree of GFD difficulty is associated with reductions in patient wellbeing and psychological distress that the dietician is critically placed to address.

Are patients with coeliac disease seeking alternative therapies to a gluten-free diet?

Abstract: Background & Aims: The cornerstone of treatment for coeliac disease is a gluten-free diet (GFD). However, adherence to a GFD is variable. Recently investigators have been reporting their preliminary findings using novel therapies. In addition, there is a growing interest in the use of complementary or alternative medicine (CAM) in gastrointestinal illnesses. These observations suggest that patients with coeliac disease may be dissatisfied with a GFD and possibly are seeking/using alternative therapies for their disease. Our aim was to assess the satisfaction levels of adults with coeliac disease towards a GFD, their use of oral CAM and views regarding novel therapies. Methods: 310 patients with coeliac disease completed a questionnaire survey while attending their out-patient appointment. The control group comprised 477 individuals. Results : Over 40% of patients with coeliac disease were dissatisfied with a GFD. The frequency of CAM use in patients with coeliac disease was 21.6% (67/310) vs 27% in the control group (129/477), p=0.09. All patients expressed an interest in novel therapies, with a vaccine being the first choice in 42% of patients, 35% and 23% for anti- zonulin and peptidases, respectively. Universally, patients placed genetically modified wheat as the lowest preference. Conclusions: A large proportion of patients with coeliac disease are dissatisfied with a GFD. Coeliac patients are not taking CAM any more than controls, suggesting they do not view CAM as an alternative to a GFD. However, all the patients in this survey were keen to consider novel therapies, with a vaccine being the most preferred option.

A new and simple algorithm for the noninvasive assessment of esophageal varices in cirrhotic patients using serum fibrosis markers and transient elastography.

Abstract: Background and aim Noninvasive serum liver fibrosis markers and liver stiffness could be used as predictors of esophageal varices in cirrhotic patients because portal hypertension is related to liver fibrosis. The aim of this study was to compare the performance of common serum fibrosis scores and transient elastography in diagnosing esophageal varices and to propose a new algorithm for predicting large varices. Methods 231 consecutive cirrhotic patients (58.4% males, mean age 55.9 years) were enrolled. Routine biological tests were performed, so that APRI, FIB-4, Forns Index and Lok Score could be calculated. All patients underwent transient elastography and eso-gastroscopy. The diagnostic performance of the methods was assessed using sensitivity, specificity, positive predictive value, negative predictive value, accuracy, likelihood ratios and receiver operating characteristic curves. Results The Lok Score was the best among all the serum scores for diagnosing the varices. For a value higher than 0.8, it had a 45.5% positive predictive value, 86.4% negative predictive value and 67.72% diagnostic accuracy for prediction of large varices. For liver stiffness higher than 30.8KPa, the positive predictive value was 47.3%, negative predictive value 81% and diagnostic accuracy 68.32%. Using both tests simultaneously, the presence of large varices was predicted with a diagnostic accuracy of 78.12%, obtaining an increment in NPV and -LR up to 93.67% and 0.21, respectively. Conclusion The Lok Score is a good predictor for excluding the presence of large varices in cirrhotic patients, similarly with liver stiffness. The two methods can be successfully combined into a noninvasive algorithm for the assessment of esophageal varices in cirrhotic patients.

Pancreatic cyst fluid analysis--a review.

Abstract: An increased number of pancreatic cysts are being diagnosed due to the increased usage of cross-sectional imaging. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) cytology and molecular analysis of these cystic lesions have led to their better detection and characterization. The aim of this review is to assess the value of cyst fluid analysis for the differential diagnosis of pancreatic cystic lesions, in view of the recent progresses of molecular analysis methods. Pancreatic cysts can be either simple (retention) cysts, pseudocysts and cystic neoplasms, while these are further subdivided into serous cystadenomas, mucinous cystic neoplasms (MCNs) or intraductal papillary mucinous neoplasms (IPMNs). EUS is now being used to investigate cystic pancreatic lesions, particularly by means of EUS guided cyst aspiration and sampling of the cyst wall or septa, as well as mural nodules. Cyst fluid can be further studied after aspiration in order to analyze cytology, viscosity, extracellular mucin, other tumor markers (CEA, CA 19-9,CA 15-3, Ca 72-4, etc.), enzymes (amylase, lipase), as well as DNA analysis of DNA quality/content or mutational analysis to study allelic imbalance/LOH (loss of heterozygosity) and K-ras mutations. After careful review of the published studies, a conclusion was reached that the use of tumor and molecular markers in conjunction with multimodality detection methods such as CT, MR and EUS-FNA allows risk stratification, while being also cost-effective.

Hepatotoxicity by bosentan in a patient with portopulmonary hypertension : a case-report and review of the literature

Abstract: Bosentan is an endothelin receptor antagonist approved for treatment of pulmonary arterial hypertension. Mild liver reactions occur in about 10% of treated patients but severe hepatotoxicity is rare. We present clinical data and treatment outcome of a severe drug induced liver injury due to bosentan in a patient with non-cirrhotic portopulmonary hypertension. After 18 months of uncomplicated therapy with bosentan 125 mg b.i.d., the patient developed a severe mixed hepatic injury. Serum levels of bilirubin were 316 µmol/l (ref. value <20 micromol/l), AST 14 µkat/l (ref. value < 0.9 µkat/l), ALT 10 µkat/l (ref. value < 0.9 µkat/l), ALP 8 µkat/l (ref. value <1.8 µkat/l) and INR 1.8 (ref. value 0.9-1.1). Complete diagnostic work-up disclosed no other cause of hepatotoxicity. Treatment with prednisolone 40 mg/day in tapering doses was ultimately added and the patient made a full recovery. Subsequent treatment with sildenafil and ambrisentan for pulmonary arterial hypertension was well tolerated and liver function tests have remained normal during 12 months' follow-up. A review of the literature revealed three other women with severe hepatotoxicity due to bosentan. Bosentan may cause severe liver injury, even after long uneventful therapy, and current recommendations on regular monitoring of liver function tests are reinforced. Ambrisentan may be a therapeutic alternative in patients with pulmonary arterial hypertension and hepatotoxicity by bosentan.

Characteristics and treatment strategy of hepatic angiomyolipoma: a series of 94 patients collected from four institutions.

Abstract: Aim To report on a Chinese multicenter series of hepatic angiomyolipoma (HAML) patients and to study the characteristics and the treatment strategy of the disease Method Data of 94 patients diagnosed with HAML from four institutions of China between December 1997 and January 2008 were reviewed retrospectively Immunohistochemical assays were performed on the surgical specimens and follow up studies were done in all the patients Results 52 of 94 patients (553%) showed no significant clinical symptoms There were no specific findings on laboratory examinations The correct preoperative diagnostic rate of ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) was 0% (0/94), 157% (11/70) and 227% (10/44), respectively Regarding the treatment, 93 patients had a hepatectomy and 1 patient was treated by radiofrequency ablation The postoperative pathology showed HAML in all the patients: 69 patients were studied with HMB-45 staining by immunohistochemistry and the positive rate was 100% The postoperative follow-up rate was 915% (86/94), no sign of recurrence or metastasis was observed during the follow-up period Conclusion This is the largest HAML series reported in the literature There are no specific signs and symptoms in HAML patients; the preoperative imaging diagnosis (including CT, MRI) is insensitive The common pathological features include the basic histological components and expression of HMB-45 Conservative treatment is not suggested; surgical resection should be considered as a treatment choice for HAML

CT and MR imaging of hepatocellular carcinoma.

Abstract: Hepatocellular carcinoma (HCC) is the fifth most common tumor in the world and the incidence is expected to increase in the future due to hepatitis viral infections and increasing cirrhosis incidence. The diagnosis of HCC is no longer based on biopsy especially in cases when curative treatment is possible. The imaging criteria are usually based on the vascular findings of HCC (e.g. early arterial uptake followed by washout in the portovenous and equilibrium phase). However, there are several limitations of the assessment of HCC by using only the vascular criteria. The use of tissue-specific contrast agents, including superparamagnetic iron oxides and hepatobiliary contrast agents, improves lesion detection and characterization. Therefore, an accurate diagnosis of HCC implies, at this moment, a combination of vascular and cellular information. This review focuses on the most important findings provided by the unenhanced and dynamic-enhanced CT and MR images regarding HCC evaluation. We also discuss the various imaging characteristics of HCC at MR imaging after the administration of tissue specific contrast agents.

A pharmacogenetics study of TPMT and ITPA genes detects a relationship with side effects and clinical response in patients with inflammatory bowel disease receiving azathioprine

Abstract: BackgroundA 95%CI 1.752-38.87, p=0.0041), as well as between mutant TPMT alleles and myelosuppression (OR 7.5; 95%CI 1.4456-38.91, p=0.0304). Conclusions: There is a positive correlation between c.94C>A variant on ITPA with clinical response. Mutant alleles on TPMT and the variant c.94C>A on ITPA gene predict side effects induced by AZA in our population (myelosuppression and arthralgia).

Herpes simplex virus hepatitis - it's high time we consider empiric treatment.

Abstract: Fulminant hepatitis is an uncommon complication of herpes simplex virus infection. Patients at risk, in particular pregnant women and immunosuppressed patients presenting with fulminant liver failure, receiving delayed acyclovir intervention may lose significant liver parenchyma prompting the need for liver transplantation. The diagnosis is often not straight forward due to the lack of specific signs or symptoms, while many patients are diagnosed at autopsy. Although herpes simplex virus associated fulminant hepatic failure carries a high mortality risk, early intervention with acyclovir may prove to be life saving. In fact, acyclovir given in the early stages of fulminant hepatic failure may prevent mortality and avoid the need for liver transplantation. We report here two pregnant women with fulminant herpes simplex virus hepatitis in whom a difference of a few hours in the initiation of empirical treatment made a vast difference to their hospital stay. The above results demonstrate a significant impact to fulminant hepatic failure and should prompt clinicians to consider empiric acyclovir therapy for at risk patients.

Usefulness of contrast enhanced ultrasound guidance in percutaneous biopsies of liver tumors.

Abstract: The performance of percutaneous echoguided biopsy in hepatic tumor diagnosis is limited by several factors, among which tumor characteristics such as tumor type, size and location play an important role. With all the advantages offered by ultrasound guidance, the overall sensitivity of this method in the tumor diagnosis has remained around 90%. Contrast enhanced ultrasound (CEUS) guided percutaneous biopsy is a new developed technique aimed at increasing the accuracy of percutaneous biopsies. With new ultrasound devices comprising the split-screen mode, which displays both the CEUS and background B-mode US image simultaneously on a single monitor, the procedure is now technically feasible. CEUS guided percutaneous liver biopsy should be applied in large tumors with consistent necrosis, in hypovascular tumors or in those invisible or poorly visible to conventional ultrasound. An increased accuracy was demonstrated in poorly visible or invisible hepatic lesions and when CEUS was used before biopsy.

Predictive factors for nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD).

Abstract: Aims The aim of our study was to assess the clinical and biological parameters associated with Nonalcoholic steatohepatitis (NASH) and to establish the predictors of significant fibrosis in Nonalcoholic fatty liver disease (NAFLD) patients. Methods We correlated clinical and biochemical parameters with histological features (simple steatosis or steatohepatitis) in 97 patients with NAFLD admitted to the University Hospital Bucharest for persistently raised aminotransferase levels. The biochemical parameters included lipid profile, glucose, liver tests and insulin. The Homeostatic Metabolic Assesment (HOMA)-index and the oxidative stress were also evaluated. Factors associated with NASH and severe fibrosis (F≥=3) were identified using the Mann-Whitney U test and multivariate analysis. The overall validity was measured using the area under receiver operating characteristic curve (AUROC) with 95% CI. Results At univariate analysis, age, BMI, splenic longitudinal diameter (SLD), HOMA, gamma glutamyl transpeptidase, C- reactive protein (CRP), albumin and INR were significantly associated with histologically proven NASH. The multivariate analysis identified four independent predictive factors for the presence of NASH: CRP (p=0.004), SLD (p=0.018), HOMA (p=0.03) and albumin level (p=0.041). The variables independently associated with severe fibrosis were albumin (p=0.008), blood glucose (p=0.017) and BMI (p=0.048). Conclusion A predictive model that incorporates the clinical and biological parameters may identify at-risk patients with NAFLD, avoiding liver biopsy on a routine basis.

Primary clarithromycin resistance in Helicobacter pylori: the Multicentric Italian Clarithromycin Resistance Observational (MICRO) study.

Abstract: Background Primary clarithromycin resistance markedly reduces Helicobacter pylori eradication rate following standard therapies. Prevalence of primary clarithromycin resistance in H. pylori is increasing, and three point mutations are mainly involved. AIM. To assess both the prevalence of primary clarithromycin resistance in Italy, and the distribution of the involved point mutations. Methods Primary clarithromycin resistance was assessed by TaqMan real-time polymerase chain reaction on antral biopsies of 253 consecutive, H. pylori infected patients enrolled in 13 Italian centres between January and September 2010. Results Primary clarithromycin resistance was detected in 25 (9.9%) patients, with prevalence values widely ranging from 0 to 25%. Clarithromycin resistance rate was higher in female as compared to male patients (13.4% vs. 5.3%, p=0.03), and it tended to be higher in non-ulcer dyspepsia than in peptic ulcer patients (10.6% vs. 6.9%, p=0.5), female patients with non-ulcer dyspepsia showing the highest value (15.4%). The A2143G point mutation was detected in 13 (52.0%) patients, the A2142G in 9 (34.6%), whilst a double point mutation (A2143G plus A2142G) in 3 (11.6%) cases. Conclusions Primary clarithromycin resistance is highly variable in different Italian geographic areas. High resistance rates were observed in female and in dyspeptic patients. Among the three point mutations of clarithromycin resistance, the A2143G remains the most frequently observed.

Combined cardiac surgery and liver transplantation: three decades of worldwide results.

Abstract: Background: Patients with end-stage-liver-disease (ESLD) require orthotopic liver transplantation (OLT) as treatment. However, cirrhotic cardiomyopathy can be clinically revealed during OLT, with the possible development of a transient overt congestive heart failure. A number of patients require a combined procedure of liver transplantation and heart surgery, which includes heart transplantation, aortic valve replacement or coronary artery bypass grafting. Indications for combined liver-heart transplantation include heart failure with associated cardiac cirrhosis, familial amyloidosis, familial hypercholesterolemia and hemochromatosis, and homozygous β-thalassemia. m ethods/ Results. We performed a thorough research of Pubmed/ Medline, gathering and discussing data concerning this clinical condition and its treatment. Conclusion: In patients with end-stage liver disease, who are unable to tolerate an OLT post-operatively due to cardiac dysfunction, combined cardiac surgery and OLT appears to have certain advantages.

Capsule endoscopy in patients with cardiac pacemakers and implantable cardioverter-defibrillators - a retrospective multicenter investigation.

Abstract: BACKGROUND & AIMS Capsule endoscopy (CE) is an established tool for the investigation of the small intestine. The Food and Drug Administration, Given Imaging and Olympus have not recommended the use of capsule endoscopy in patients with cardiac pacemakers and implantable cardioverter defibrillators (ICDs). The aim of this retrospective study was to investigate the safety of capsule endoscopy systems (Given Imaging and Olympus) when applied in patients with different types of pacemakers/ICDs in vivo. METHODS A standardized questionnaire was sent to high volume centers in Germany and in Austria. The questionnaire covered the age and gender of the examined patients, indication of CE, brand and type of CE, brand and model of pacemaker/ICD, check of the devices before and after CE, monitoring during CE, possible interference between CE and cardiac pacemakers/ICDs and possible adverse events during CE. RESULTS Data from 62 patients were retrieved for this study. Capsules used were Given Imaging (n=58; M2A, M2Aplus, PillCam SB2), Olympus EndoCapsule (n=3), Given PillCam Colon (n=1). The collective included patients with pacemakers/ICDS from seven brands (Biotronik, Medtronic, St. Jude Medical, Guidant, Boston Scientific, Ela Sorin, Vitatron) with a total of 19/8 (pacemaker/ICD) different types. In two patients interference between capsule endoscopy and telemetry (loss of images/gaps in video) was recorded. None of the cardiac pacemakers or ICDs was impaired in function. No clinically evident event was observed in any of these patients. CONCLUSIONS Clinical use of these CE types is safe in patients with cardiac pacemakers and ICDs. Interference can occur between CE and ECG-telemetry leading to loss of images or impaired quality of video.

Interleukin-16 (IL-16) gene polymorphisms in Iranian patients with colorectal cancer.

Abstract: Background & Aims: A number of theories have been put forward to clarify the etiology of colorectal cancer (CRC), such as genetic alterations and cytokine production. A combination of inflammatory cytokines has an important role in cancer development. The aim of our study was to screen for alterations located in promoter and exons of IL-16 gene sequence, to determine the distribution of genotypes in individuals with CRC and healthy controls in a sample of Iranian population. m ethods : The case group consisted of 260 individuals with colorectal cancer and the control group included 405 healthy individuals. Three IL-16 gene polymorphisms (rs4072111, rs11556218, rs4778889) were genotyped using PCR-RFLP method. RFLP results were confirmed by direct sequencing. Results: A significant association between rs11556218 SNP in the IL-16 gene and the risk of CRC was found. The TG genotype of rs11556218 T/G polymorphism showed significant association with a 1.75 fold increased risk of CRC (P=0.005; adjusted OR: 1.759; 95% CI: 1.191- 2.598). In addition a significant association between CC genotype of rs4778889 T/C polymorphism and decreased risk of CRC in male subjects (P=0.045; adjusted OR: 0.192; 95% CI: 0.038-0.967) was determined. Conclusion: This study is the first report of IL-16 gene polymorphisms among CRC patients from Iran. Our results suggest an influence of rs11556218 T>G and rs4778889 T/C polymorphisms on the altered risk of CRC.

Response to first intravenous steroid therapy determines the subsequent risk of colectomy in ulcerative colitis patients.

Abstract: Background & Aims. A severe flare-up develops in approximately 15% of patients with ulcerative colitis (UC). It is questionable whether the response to the first parenteral corticosteroid therapy decreases the risk for colectomy. Our aim was to evaluate the association between long-term colectomy rate and the efficacy of steroids in the first few days of the therapy and to assess other predictive factors for colectomy in our patients hospitalized because of the first severe attack of UC.Patients and methods. The records of the first hospitalization of a total of 183 UC patients with severe exacerbation were reviewed. Every patient had received parenteral corticosteroid treatment. Colectomy was performed in refractory UC or in the case of intolerable side-effects of the rescue therapy. We compared different laboratory and clinical parameters between patients undergoing colectomy and those who avoided surgery.Results. Clinical response to steroid therapy was achieved in 110 of the 183 patients with acute severe UC; 14.5% of steroid responder patients were operated on during the follow-up period. 39.7% of patients in the steroid-refractory group required either urgent or late colectomy. The overall colectomy rate was 24.6%. Unresponsiveness to intravenous steroid therapy, anemia, and the need for blood transfusion proved to be the major predictors for colectomy.Conclusion. The colectomy rate was 2.5 times higher in our patients with acute severe UC not responding to the intensive steroid therapy, suggesting that the response to the therapy of the first 3-5 days of hospitalization may determine the long-term outcome and colectomy rate in UC.

The infectious complications of interventional radiology based procedures in gastroenterology and hepatology.

Abstract: Background and aims Many interventional radiology (IR) procedures are used to manage gastroenterological and hepatobiliary diseases. One of the most common complications of any IR procedure is infection. Methods Literature published in English from January 1960 to August 2010 pertaining to the infectious complications of IR in gastroenterology and hepatology patients was examined by electronic search (Medline and the National Library of Medicine, Embase and the Cochrane Library). Results Percutaneous transhepatic cholangiogram (PTC) and biliary drainage, trans-arterial chemoembolization (TACE), transjugular intrahepatic portosystemic shunting (TIPS), imaged guided drainage of an intra-abdominal abscess and radiologically inserted gastrostomy (RIG) are the most common IR procedures performed for gastroenterology and hepatology patients. Procedures such as PTC have a high rate of infection. Infectious complications of TACE and TIPS are uncommon but when they occur, they can be devastating. RIG procedures are also rarely complicated by infection and such infections are generally mild. Use of prophylactic antibiotics is recommended for most of the above procedures. Conclusion The increased availability of IR based gastrointestinal and hepatobiliary techniques means that their related infectious complications will inevitably become more common. It is vital that clinicians be aware of the aetiology, timing and treatment of any potential infections in the peri-procedure period.

Endoscopic ultrasound: current role and future perspectives in managing rectal cancer patients.

Abstract: As therapeutic regimens for rectal cancer have seen considerable changes, an accurate staging is mandatory for choosing the adequate strategy Locoregional staging is the decisive factor in selecting patients for neoadjuvant chemoradiation therapy and for determining the extent of surgery Endoscopic ultrasound (endorectal ultrasound--ERUS) is a very effective method for assessing the local extent of rectal cancer, especially regarding the depth of tumor infiltration Although a significant limitation is represented by its lower accuracy for diagnosis of lymph node metastases, this is still a point of concern for other imaging tests as well In this review we report the current data on ERUS, presenting both its advantages and limitations, and making a comparison to other staging methods Recent developments of the technology that might enhance staging accuracy are also discussed

Use of elderly donors for liver transplantation: has the limit been reached?

Abstract: Background and aim Several solutions have been proposed for the minimization of both organ shortage and prolonged waiting time for liver transplantation (LT): expansion of the donor pool using elderly donors represents a possible solution. However, it is still not fully explained if the use of "extreme" donors could cause inacceptable post-transplant adjunctive risks. The aim of the study is to evaluate the impact of donor age on post-LT patient and graft survival. Methods A cohort of 188 LTs were stratified in four groups according to donor age (Group 1: age Results No differences were observed among the groups with regard to initial ( Conclusions Use of > 70 year-aged donors should be considered with caution and only in selected cases.

Carcinosarcoma of the pancreas: a unique case with emphasis on metaplastic transformation and the presence of undifferentiated pleomorphic high-grade sarcoma.

Abstract: We report a rare case of pancreatic carcinosarcoma in a 48-year-old man. An abdominal ultrasound scan incidentally detected a large heterogeneous mass in the left upper quadrant. CT and MRI scans indicated a rapidly growing unilocular cystic mass in the pancreatic tail. Grossly, the resected pancreatic mass measured 7×5×5 cm and consisted of a unilocular cystic lesion that had several solid mural nodules. Microscopically, the cystic wall showed two carcinomatous components, mucinous cystadenocarcinoma and anaplastic carcinoma. The solid lesion predominantly consisted of pleomorphic spindle cells arranged in interlacing fascicles which had infiltrated the adjacent pancreatic parenchyma. In some areas of this sarcomatous component, anaplastic carcinoma cells intermingled with or transformed into spindle cells. Immunohistochemically, the carcinomatous components were strongly positive for epithelial markers, and transforming anaplastic carcinoma cells were immunoreactive for both epithelial markers and vimentin; in contrast, the sarcomatous component was strongly positive for only vimentin. Additionally, an identical mutation (G to A transition) at codon 12 of K-ras gene and concordant immunoreactivity for p53 protein were detected in the carcinomatous and sarcomatous components. These findings suggested that the pancreatic carcinosarcoma could be of monoclonal origin, and that the sarcomatous component might have arisen from metaplastic transformation of the carcinomatous component.

Alcohol Dehydrogenase (ADH) and Aldehyde Dehydrogenase (ALDH) as Candidates for Tumor markers in Patients with Pancreatic Cancer

Abstract: Background: Various alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) exist in the pancreas. Moreover, ADH and ALDH are present in pancreatic cancer cells. The activity of ADH class III isoenzymes is significantly higher in cancerous than in healthy tissues. The expression of these enzymes in cancer cells is reflected by increased enzyme activity in the sera and thus could be helpful for diagnosing pancreatic cancer. The aim of this study was to investigate the potential role of ADH and ALDH as tumor markers for pancreatic carcinoma. methods: Serum samples were taken from 165 patients with pancreatic cancer and 166 healthy controls. Total ADH activity and class III and IV isoenzymes were measured by photometric and ALDH activity, ADH I and II by the fluorometric method. Results: There was a significant increase in the activity of ADH III isoenzyme (14.03 mU/l vs 11.45 mU/l; p < 0.001) and total ADH activity in the sera of pancreatic cancer patients compared to the control. The diagnostic sensitivity for ADH III was 70%, specificity 76%, positive and negative predictive values were 79% and 71% respectively. Area under ROC curve for ADH III was 0.64. Conclusion: The results suggest a potential role for ADH III as a marker of pancreatic cancer.

Plasma or serum TIMP-1 is a predictor of survival outcomes in colorectal cancer: a meta-analysis.

Abstract: BACKGROUND AND AIMS Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a small secretory glycoprotein with anti-apoptosis and anti-matrix metalloproteinase activity. There have been some discordant data regarding the value of TIMP-1 as a prognostic factor in colorectal cancer (CRC) patients. To address this controversy, we conducted a meta-analysis for the relationship between TIMP-1 levels and overall survival in CRC. METHODS We selected the relevant published studies using citation databases including PubMed, Science Citation Index, and Conference Papers Index. The effect sizes of TIMP-1 on the patient's overall survival and TNM stages were calculated by hazard ratio (HR) or odds ratio (OR), respectively. The effect sizes were combined using a random-effects model. RESULTS Survival outcomes between high and low plasma or serum TIMP-1 levels were compared by uni- and multivariate analyses involving 1,477 and 1,359 CRC patients, respectively. CRC patients with high plasma or serum TIMP-1 levels showed poor survival rates compared to patients with low plasma or serum TIMP-1 in the uni- and multivariate analyses (HR, 2.2 and 2.1; P < 0.001). In addition, high TIMP-1 expression in colon cancer tissues was significantly associated with worse survival outcomes in 438 CRC patients (HR = 1.4; P = 0.017). CONCLUSION Plasma or serum TIMP-1 levels predict survival outcomes of CRC patients.

Clinicopathological correlations of nestin expression in surgically resectable pancreatic cancer including an analysis of perineural invasion.

Abstract: Background & Aims: Nestin is considered to be a marker of stem/progenitor cells in different tissues. Nestin expression was also described in various tumors. In pancreatic ductal adenocarcinoma (PDAC), its role in cancer cell migration, invasion, and metastases has been suggested. The study aimed at examining the expression of nestin in PDAC, and to evaluate its clinicopathological correlations. m ethods : The expression of nestin was immunohistochemically examined in 117 PDAC resection specimens, analyzed, and correlated with clinico-pathological parameters including perineural invasion (PNI). Analysis of nestin expression in nerve fibers in tissues of chronic pancreatitis (CP) was added. Results: Immunohistochemical analysis of nestin expression showed 79 nestin negative (67.5 %) and 38 nestin positive (32.5 %) PDACs. No significant correlations of nestin expression in tumor cells with the analyzed clinicopathological parameters were demonstrated. Tumor grade (p<0.001) and nodal status (p=0.009) proved to represent independent prognostic factors. PNI was identified in 94 PDAC (80.3 %), and did not correlate with nestin expression. Nestin immunostaining was displayed in nerve fibers of both CP and PDAC tissues. Conclusion: An intimate link of nestin to a biological process of pancreatic cancer was confirmed. The expression of nestin did not prove to be a valuable prognostic factor and an immunohistochemical assessment of nestin expression is not superior to conventional prognostic factors in PDAC. A correlation between nestin expression in tumor cells and PNI was not confirmed and expression of nestin in nerve fibers of both PDAC and CP tissues seems to reflect the process of neural remodeling responsible for pancreatic neuropathy.

Weight-based dosing regimen of peg-interferon α-2b for chronic hepatitis delta: a multicenter Romanian trial.

Abstract: BACKGROUND Antiviral therapy for chronic hepatitis D (delta) is not yet satisfactory, although it appears to be the only means to alter the progressive natural course of chronic hepatitis D virus (HDV) infection. AIM To assess safety and efficacy, evaluated by virological, biochemical and histological end-of-treatment (EOT) and end-of-follow-up (EOF) response to peg-interferon α-2b 1.5 µg/kg body weight weekly in a Romanian cohort of naive patients with chronic hepatitis delta. RESULTS 49 Caucasian patients (55.1% men, 44.9% females) with a mean age of 37.95 years received study medication; per-protocol population consisted of 36 subjects. Virological EOT response was present in 33.3% and EOF response was maintained in 25% of patients. 50% of study population showed normalization of ALT level at EOT and 25% at EOF. A combined biochemical and virological response was observed in 19.4% of patients at EOT and in 16.7% at EOF. At baseline, the necroinflammation quantified by histological activity index (HAI) score was 9.72 and the mean fibrosis score was 2.03; there was a significant decrease of HAI score to 7.44 (p=0.01) at EOT, but not for fibrosis score (1.33, p=0.37). However, only 8.3% of patients at EOT and 19.4% at EOF had progressive histological disease. CONCLUSIONS Treatment with peg-interferon α-2b succeeded in obtaining a negative HVD RNA in 25% of patients after 104 weeks of follow-up, although combined biochemical and virological response was present in only 16.7%. Necroinflammation decreased significantly in treated patients. Longer treatment periods with pegylated interferon or combination regimen peg interferon-nucleotide analogues should be tested in order to increase efficacy.

Gallstones and liver disease: an overview.

Abstract: Gallstones (GS) may form as a result of many different disorders. Two main categories of gallstones can be identified according to their predominant chemical composition: cholesterol and pigment stones. Unphysiological biliary supersaturation from hypersecretion of cholesterol, gallbladder hypomotility and the accumulation of mucin gel contribute to the formation of cholesterol GS, while black pigment stones derive from the precipitation of calcium hydrogen bilirubinate where pigment supersaturation and deposition of inorganic salts, phosphate and calcium bicarbonate accelerate the nucleation. Pigment supersaturation is common in hemolytic disorders, enterohepatic cycling of unconjugated bilirubin and ileal disorders and/or surgery [1]. There is also a third main type of GS, very common in East Asia: brown pigment stones, which form in the bile ducts due to bile stasis, parasites, uncomplete polymerization of calcium hydrogen bilirubinate, saturated fatty acids and bacterial infection with enzymatic hydrolysis of biliary lipids. In the general population, one of the main risk factors for developing GS is the sex: GS are more common in women than in men. Other factors are age, genes, race the burden of GS disease is epidemic in American Indians (60-70%), decreases in Hispanics of mixed Indian origin and is further reduced in Black Americans [2]. Additional factors are obesity, rapid weight loss, glucose intolerance, insulin resistance, high dietary glycemic load, alcohol use, diabetes mellitus, hypertriglyceridemia, drugs, pregnancy. Nowadays, there is much interest in discovering the relationship between GS and liver disease and in the last issue Coelho and colleagues [3] decided to assess the prevalence of cholelithiasis in patients undergoing liver transplantation EDItORIAL

The safety of endoscopic ultrasonography-guided drainage of pancreatic fluid collections without fluoroscopic control: a single tertiary center experience.

Abstract: BACKGROUND Endoscopic ultrasonography (EUS) is preferred for guiding drainage of pancreatic fluid collections, with a success rate exceeding 90% when fluoroscopy is used. When fluoroscopy cannot be used, drainage can still be performed, but no data regarding the safety of such a procedure have yet been published. AIM To establish the safety of EUS-guided drainage without fluoroscopic control and to identify criteria for the selection of suitable patients. METHODS The pancreatic fluid collections considered suitable for EUS-guided drainage were >5 cm in diameter, symptomatic, without ductal communication. We attempted EUS-guided drainage of PC prospectively in 24 patients: 9 with abscesses and 15 with pseudocysts. RESULTS Drainage was successful in 20 cases (83.3%), with complete resolution after a median 18 months' follow-up. EUS-guided drainage failed in four patients (16.7%): one in the abscess group due to symptomatic pneumoperitoneum and three in the pseudocyst group due to thick wall. Drainage failure was associated with a diameter 2 mm and was considered to be due to the sliding of the cystotome on the pseudocyst wall. During follow-up there was one procedure unrelated death (4.1%) and no pancreatic fluid collections relapses. CONCLUSIONS Fluoroscopic control represents a helpful tool, but it is not always necessary for EUS-guided drainage of pancreatic fluid collections. EUS-guided drainage is possible, efficient and safe without fluoroscopy in selected pancreatic fluid collections with a diameter larger than 6 cm and a thin wall. Collections with a thick wall should be drained under fluoroscopy or referred directly for surgery.

Appropriateness of the indication for colonoscopy: systematic review and meta-analysis

Abstract: Background and aims Application of appropriate indications for colonoscopy (OC) should conserve limited endoscopic resources. To perform a systematic review and meta-analysis to assess the accuracy of ASGE and EPAGE guidelines in selecting patients referred for OC, relative to the detection of neoplastic and non-neoplastic relevant endoscopic findings. Methods Studies comparing the appropriateness of OC indication according to ASGE or EPAGE guidelines and the detection of cancer, adenomas, and benign relevant endoscopic findings were identified by searching MEDLINE (1982 - June 2009). Predefined outputs of the meta-analysis were sensitivity, specificity, positive and negative likelihood ratios (LR+, LR-), and the diagnostic odds ratio (DOR). Results We included twelve cohort studies comprising 14,160 patients; 10,056 OC indications were categorized as appropriate, and 3,522 (26%) as inappropriate. For cancer detection, the weighted sensitivity, specificity, LR+, LR- and DOR were 89% (95% CI, 82-93%), 26% (95% CI, 21-31%), 1.2 (95% CI, 1.1-1.3), 0.45 (95% CI, 03-0.7), and 3 (95% CI, 1-5), respectively. For adenomas, the adjusted sensitivity, specificity, LR+, LR- and DOR were 85% (95% CI, 77-91%), 27% (95% CI, 22-32%), 1.14 (95% CI, 1-1.2), 0.6 (95% CI, 0.4-0.9), and 1.9 (95% CI, 1.2, 2.9), being for relevant findings equal to 89% (95% CI, 82-93%), 26% (95% CI, 21-31%), 1.16 (95% CI, 1-1.3), 0.44 (95% CI, 0.25-0.8), and 2.6 (95% CI, 1.2-5.6). Conclusions Appropriateness guidelines appeared to have a suboptimal sensitivity and a poor specificity for colorectal cancer, being also characterized by a similar accuracy for the diagnosis of benign relevant endoscopic findings. Better strategies are required to select patients with significant pathology for OC.

Response to standard of care antiviral treatment in patients with HCV liver cirrhosis - a systematic review.

Abstract: BACKGROUND Patients with HCV liver cirrhosis are a category difficult to treat. The aim of this study was to establish the sustained virological response (SVR) rates in HCV patients with liver cirrhosis treated with standard of care therapy (Pegylated Interferon and Ribavirin for 48 weeks in genotypes 1 and 4 and 24 weeks in genotypes 2 and 3). METHODS Searching the PubMed, Medline, Lilacs, Scopus, Ovid and Medscape databases we identified all the articles published until February 2011 that included only HCV cirrhotic patients. These studies evaluated the SVR after standard of care treatment: Pegylated Interferon alpha 2a (doses ranging between 135-180 µg/week) or Pegylated Interferon alpha 2b (1 or 1.5 µg/kg/week) and Ribavirin (doses ranging between 800-1200 mg/day). We used the following key words: HCV, liver cirrhosis, sustained virological response (SVR). RESULTS The overall SVR rate was 33.3% (95%CI-confidence interval=30.6-36.2%). SVR was significantly higher in patients with genotypes 2 and 3 (422 patients) as compared to those with genotypes 1 and 4 (692 patients): 55.4% (95%CI=50.7-60.1) versus 21.7% (95%CI=18.7-25), p < 0.0001. CONCLUSION The overall SVR rate in cirrhotic patients treated with standard of care therapy is 33.3%, but lower in cases affected by genotypes 1 and 4 (21.6%) which makes them a priority regarding the development of more potent drugs for effective treatment.

Adalimumab-induced lupus erythematosus with central nervous system involvement in a patient with Crohn's disease.

Abstract: The anti-tumor necrosis factor (TNF) agents are drugs that in recent years turned out to be a mainstay of therapy for the treatment of inflammatory bowel disease. Nevertheless, they have several adverse effects such as infectious complications and immunogenicity. One of the most common immunogenic effects is the development of autoantibodies, mainly anti-nuclear antibodies and anti-double-stranded DNA antibodies, only rarely associated with overt clinical manifestations of systemic lupus erythematosus. Adalimumab is a fully humanized monoclonal antibody widely used for the treatment of Crohn's disease and supposed to have less immunogenic activity and a safer profile than other anti-TNF agents. The occurrence of systemic lupus erythematosus with involvement of the central nervous system appears to be a very rare complication of such drugs, and no cases have been reported in the medical literature in patients treated with adalimumab. We report a case of a 53 years-old woman with ileo-colic Crohn's disease where the treatment with adalimumab was complicated by systemic lupus erythematosus with central nervous system vasculitis.